Hypermethylation of TMEM240 Predicts Poor Hormone Therapy Response and Disease Progression in Breast Cancer

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題名:	Hypermethylation of TMEM240 Predicts Poor Hormone Therapy Response and Disease Progression in Breast Cancer
作者:	洪進昇 Lin, Ruo-Kai;Su, Chih-Ming;Lin, Shih-Yun;Thu, Le Thi Anh;Liew, Phui-Ly;Chen, Jian-Yu;Tzeng, Huey-En;Liu, Yun-Ru;Chang, Tzu-Hao;Lee, Cheng-Yang;Hung, Chin-Sheng
貢獻者:	醫學系外科學科
關鍵詞:	Breast cancer;Cell motility;Circulating cell-free DNA;DNA methylation;Disease progression;MetaCore and hormone therapy;Proliferation;RNA-seq;TMEM240;Tumor suppressor genes.
日期:	2022-06
上傳時間:	2024-12-04 14:04:51 (UTC+8)
摘要:	Background: Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression. Methods: Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP); real-time reverse transcription PCR; and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation; viability; migration assays; RNA-seq; and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells. Results: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240; which is localized to the cell membrane and cytoplasm; represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients; the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response; especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression; whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity; 93.1% specificity; and 90.2% accuracy. Conclusions: Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.
關聯:	Molecular medicine (Cambridge; Mass.); 28(1); 67.
描述:	【112-2 升等】臺北醫學大學教師升等專門著作職別：專任送審等級：教授著作送審
附註:	代表著作名稱：《Hypermethylation of TMEM240 Predicts Poor Hormone Therapy Response and Disease Progression in Breast Cancer》 ? 2022. The Author(s).
資料類型:	article
顯示於類別:	[教師升等送審著作] 112 [外科學科] 期刊論文

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